Relation Between Interleukin-6, Interleukin-10 And Interleukin-2 Receptor And Mortality In Severely Ill COVID-19 Patients.

Objectives: To investigate the relation involving soluble interleukin-2 receptor, interleukin-6 and interleukin-10 in hospitalised patients with severe coronavirus disease-2019 infection. Method: This single-centre cohort study was conducted at the Kafrelshiekh University Hospital, Egypt, from January to June 2022, and included all patients of either gender who were hospitalised with severe infection with the coronavirus disease-2019 isolation ward. Chemiluminescence immunoassay method was used to measure levels of procalcitonin, ferritin, soluble interleukin-2 receptor, interleukin-6 and interleukin-10. Data was analysed using SPSS version. 25. RESULTS: Of the 250 patients with median age 57.5 years (interquartile range: 45.8-66.0 years), 147(59%) were males and 103(41%) were females. Of them, 102(40.8%) patients died; 68(66.7%) males, 34(33.3%) females, median age 60.0 years (interquartile range: 48.8-70.0). Among the 148(59.2%) survivors, 79(53.4%) were males and 69(46.6%) were females, while the overall median age was 55.0 years (interquartile range: 41.5-65.8 years). The survivors had significantly lower levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 (p<0.001). Correlation analysisidentified significant positive correlation between IL-2R, IL-6 and IL-10 levels and almost all the inflammatory and coagulation parameters, including C-reactive protein, lactate dehydrogenase, procalcitonin, ferritin, D-dimer and fibrinogen (p<0.05). CONCLUSIONS: Elevated levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 were found to be associated with greater risk of mortality in coronavirus disease-2019 patients.

Peripheral blood and hepatic Toll-like receptor 7 expression and interferon lambda 1 levels in chronic hepatitis C: Relation to virus replication and liver injury.

BACKGROUND AND AIM: Toll-like receptor 7 (TLR7) can recognize single-stranded RNA viruses like hepatitis C virus (HCV) with subsequent induction of different interferon (IFN) types including IFN lambda (IFNL), which activate an immediate anti-viral response. However, the role of TLR7 in inflammation and fibrosis, characteristics of HCV-induced liver injury, is still controversial. The present work was designed to investigate the potential role of TLR7 and IFNL1 in chronic hepatitis C (CHC) in relation to viral replication and liver injury. METHODS: Forty two treatment-naïve patients with CHC and 20 healthy subjects were enrolled in the study. TLR7 expression on peripheral blood CD14+ monocytes was studied by color flow cytometry and the frequency of TLR7+CD14+ cells was expressed as percentage of total monocyte count. Quantification of IFNL1 levels in serum was determined using enzyme-linked immunosorbant assay. Liver biopsies were examined for assessment of histological activity grade (A0-A3) and fibrosis stage (F0-F4) according to METAVIR scoring system as well as steatosis grade. Immunohistochemical staining was performed using human antibodies against TLR7 and IFNL1 and was scored semi-quantitatively (score 0-3). Hepatic expression of TLR7 and IFNL1 was further classified using a two-grade scale as low expression (score 0 or 1) and high expression (score 2 or 3). RESULTS: Percentages of circulating TLR7+CD14+ monocytes and serum IFNL1 levels were significantly higher in patients with CHC than in healthy controls (P = 0.025 and P < 0.001 respectively) and were positively correlated with corresponding hepatic TLR7 and IFNL1 expression (P < 0.001 and P = 0.010 respectively). Significantly lower peripheral blood and hepatic TLR7 expression and IFNL1 levels were found in patients with viral loads between 200,000-600,000 IU/ml and >600,000 IU/ml than in those with viral load <200,000 IU/ml (P < 0.05), in patients with severe necroinflammation than in those with mild-to-moderate necroinflammation (P < 0.05) and in patients with advanced fibrosis than in those with early fibrosis (P < 0.01). Also, changes in TLR7 expression and IFNL1 production in peripheral blood and the liver were inversely correlated with serum levels of aspartate and alanine aminotransferases (P < 0.05) and HCV RNA (P < 0.01), histological activity grade (P < 0.01) and fibrosis stage (P < 0.01). By plotting receiver operating characteristics (ROC) curve, serum IFNL1 showed higher sensitivity and specificity than percentages of circulating TLR7+CD14+ monocytes in discriminating patients with CHC according to the severity of hepatic necroinflammation (area under the curve (AUC) = 0.901 vs. 0.816 respectively) and fibrosis (AUC = 0.971 vs. 0.825 respectively) at a cut-off value of 44.75 pg/ml and 10.25% respectively. CONCLUSIONS: TLR7 activation and IFNL1 production in CHC may play an important role in controlling viral replication and limiting hepatic inflammation and fibrosis and their downregulation may result in viral persistence and disease progression. The immunoregulatory role of TLR7-IFNL1 pathway in the pathogenesis of chronic HCV infection should be further studied. Clinical trials with a large number of patients are needed to assess the usefulness of serum IFNL1 as a potential biomarker for severity of liver injury in chronic HCV infection and other liver diseases.

Prognostic significance of complement factors in severely ill patients with COVID-19.

Coagulopathy, cytokine release, platelet hyperactivity and endothelial activation are regarded as potential major contributors to COVID-19 morbidity. Complement activation might provide a bridge linking these factors in severe COVID-19 illness. In this study, we investigated the prognostic significance of selected complement factors in hospitalized patients with severe COVID-19 infection. The study included 300 hospitalized adults with severe COVID-19 infection. Complement factors (C3, C3a, C4, sC5b-9) were assessed by commercial ELISA kits. Outcome parameters included mortality, intensive care unit admission and duration of hospital stay. It was found that survivors had significantly higher serum C3 (median (IQR): 128.5 (116.3-141.0) mg/dL vs 98.0 (70.0-112.8) mg/dL, p<0.001) and C4 (median (IQR): 36.0 (30.0-42.0) mg/dL vs 31.0 (26.0-35.0) mg/dL, p<0.001) levels when compared with non-survivors. On the other hand, it was shown that survivors had significantly lower C3a (median (IQR): 203.0 (170.3-244.0) ng/mL vs 385.0 (293.0-424.8) ng/mL, p<0.001) and sC5b-9 (median (IQR): 294.0 (242.0-318.8) ng/mL vs 393.0 (342.0-436.5) ng/mL, p<0.001) levels when compared with non-survivors. Multivariate logistic regression analysis identified C3a (OR: 0.97 (95% CI 0.96 to 0.99), p<0.001) and C4 (OR: 0.92 (95% CI 0.86 to 0.98), p=0.011) levels as significant predictors of mortality. In conclusion, serum levels of complement factors are related to mortality in severely ill patients with COVID-19.

Identifying Leukemia-associated Immunophenotypes in Acute Myeloid Leukemia Patients Using Multiparameter Flow Cytometry.

OBJECTIVES: We sought to identify leukemia-associated immunophenotypes (LAIPs) in 50 acute myeloid leukemia (AML) patients at diagnosis using an eight-color multiparameter flow cytometry (MFC) panel and to detect if they showed any alteration in relapsed/refractory cases. METHODS: We used the eight-color MFC panel with CD45/side scatter log gating strategy to analyze LAIPs in 50 AML patients presenting to Alexandria University Hospitals, Egypt at diagnosis and relapse and refractory cases. Twenty age and sex matched bone marrow samples from patients performing bone marrow aspirate for non-malignant hematological indications were included as controls. RESULTS: LAIPs were observed in 43 (86.0%) cases. Only one aberrant immunophenotype was identified in four cases (9.3%), while two to 12 aberrant immunophenotypes were found in the other 39 (90.7%) cases. Strong LAIPs were obtained by combining CD2, CD4, CD56, with either CD34 or CD117, in contrast to CD19, which has to be combined with CD117. Refractory cases showed the presence of the same LAIPs at both initial diagnosis and persistent disease. One case showed the acquisition of new LAIPs after relapse. CONCLUSIONS: The good choice of LAIPs depends on their specificity rather than their frequency. The results of this study can help in increasing the sensitivity of LAIPs strategy in minimal residual disease using MFC in AML patients, which is considered an important post-diagnosis parameter associated with prognosis and clinical outcome.

Study of microRNA Profile as a Molecular Biomarker in Egyptian Chronic Lymphocytic Leukemia.

MicroRNAs target mRNAs for cleavage or translational repression. They play a critical role in the progression of malignancies and leukemias including chronic lymphocytic leukemia (CLL). However, microRNA expression levels in Egyptian patients with CLL, and their prognostic value remain elusive. Our main aim was to assess the expression pattern of a panel of microRNAs in CLL patients to create an informative microRNA profile. The study subjects were 40 newly diagnosed CLL patients of both sexes and 40 age and sex matched controls. The expression levels of 12 microRNAs were evaluated by qRT-PCR, including miR-15a, 16, 23b, 24, 29a, 29c, 34a, 146a, 155, 181a, 195, and 221. Flow cytometry was used to determine the expression levels of BCL2, CD38, and ZAP-70 in CLL patients. We identified various degrees of upregulated miRNAs (miR-29a, miR-29c, miR-34a, miR-155, miR-146a, and miR-195) and down-regulated ones (miR-15a, miR-16, miR-23b, miR-24, miR-181a, and miR-221) in CLL patients relative to controls. The mean fluorescence intensity ratio (MFI-R) of BCL2 was recorded and was significantly upregulated in CLL patients compared with normal controls. In addition, inverse correlations were observed between microRNAs (miR-15a, miR-16, miR-155, and miR-195) and BCL2 MFI-R while positive correlations were observed between miR-29a and miR-29c, and BCL2 MFI-R. These findings suggest that these miRNAs regulate BCL2 levels. Moreover, we found that miR-15a, miR-16, miR-155, miR-181a, miR-195 and miR-221 were significantly upregulated, while miR-29a and miR-29c were significantly downregulated in ZAP-70 positive CLL patients. Various miRNAs may play an important role in the pathogenesis of CLL and have the potential to be used for the prognosis of patients with CLL.

Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases.

Circulating free DNA (CFDNA) has been shown to be a good source of liver tissue-derived DNA in African and Asian patients with chronic liver disease or HCC. In Egypt, HCC is a frequent carcinoma and mostly occur in the context of chronic infection by HCV, a widespread infection in the Egyptian population. Here we have examined the presence of mutations in TP53 at codon 249 (Ser-249, considered as a hallmark of mutagenesis by aflatoxin) and in CTNNB1 (gene encoding beta-catenin) in CFDNA of patients with HCC or chronic liver disease, from Alexandria, Egypt. The DNA concentrations were significantly higher in HCC patients compared to HBV and HCV carriers without cancer, and to sero-negative individuals. Ser-249 TP53 mutations were determined using PCR-restriction digestion (RFLP) in CFDNA of 255 subjects, and confirmed by sequencing. Ser-249 was found in CFDNA of 12 subjects (4.8%), with the highest prevalence in subjects with chronic liver disease and infection by HBV (6/36; 16.7%) Mutations in CTNNB1 were examined using PCR combined to DHPLC and followed by sequencing. No mutations were found in CTNNB1 neither in CFDNA or in tumour tissue. In parallel, studies on DNA extracted from 20 HCC biopsies showed the presence of ser-249 mutation in two cases (10%). These results indicate that mutagenesis by aflatoxin may play a role in hepatocarcinogenesis in Egypt, and CFDNA may serve as a convenient source of material in monitoring the effects of aflatoxin exposure and viral infections in chronic liver disease and cancer.

The prognostic impact of loss of chromosome 7 material detected by fluorescence in situ hybridization (FISH) in myeloid malignancies.

BACKGROUND: Monosomy 7 (-7) or deletion in its long arm [del(7q)] is among the most common chromosomal abnormalities in myeloid malignancies. There are prognostic variations between -7 and del(7q) in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). AIM: To describe the clinical characteristics, response to treatment, and survival of patients with primary AML and MDS having -7 or del(7q) detected by fluorescence in situ hybridization (FISH). PATIENTS AND METHODS: The study was conducted on 53 patients with primary AML and MDS. They were tested for chromosome 7 abnormality using FISH technique. RESULTS: Thirty-one patients had chromosome 7 abnormality and 22 did not. Lower complete remission and higher death rates were observed in patients with -7 (47.6% and 62%, respectively) when compared to patients with del(7q) (70% and 40%, respectively) with no significant difference (p = 0.218 and 0.101, respectively). The median overall survival (OS) of patients with -7, del(7q) and normal chromosome 7 were 32.0, 43.0 and 50.0 months, respectively, with significant statistical difference (p = 0.001). This difference was evident between patients with -7 and those with normal chromosome 7 (p = 0.001), and less evident between patients with -7 and those with del(7q) (p = 0.021). CONCLUSION: Chromosome 7 analysis has clear impact on the outcome of myeloid malignancies. The prognostic variations between -7 and del(7q) is attributed to multiple factors. Cases with del(7q) have better outcome than cases with -7. FISH provides a powerful tool for detecting and monitoring patients with chromosome 7 abnormalities.

Endotoxins and inflammation in hemodialysis patients.

Long-term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so-called MIA syndrome. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C-reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM-1 was estimated using enzyme-linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre-HD level of VCAM was 1851.00 ng/mL, while the mean post-HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post-HD rise in sVCAM-1.

Expression of apoptotic markers BCL-2 and Bax in chronic hepatitis C virus patients.

OBJECTIVES: Hepatitis C viral infection(HCV) influence the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. DESIGN AND METHODS: Group 1: chronic HCV patients with liver cirrhosis and ascites. Group 2: chronic HCV patients without liver cirrhosis and group 3: healthy subjects as control group. Bcl-2 and Bax expression were evaluated by flowcytometry. RESULTS: HCV patients (with cirrhosis and ascites) had a statistically significantly low Bcl-2 expression, a significantly high Bax expression and a significantly decreased Bcl-2/Bax ratio compared with controls. While, the results are inverted in the other HCV group. Both groups of HCV, Bcl-2/Bax ratio showed a significant positive correlation with Bcl-2 and a significantly negative correlation with Bax. CONCLUSIONS: Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

TP53 mutations in circulating free DNA from Egyptian patients with non-Hodgkin's lymphoma.

BACKGROUND: P53 protein plays important role in the maintenance of genome stability in mammalian cells; it acts in many processes including cell-cycle checkpoint, DNA repair, apoptosis, and angiogenesis. Mutations of P53 have been reported as common mutations in solid tumours, including non-Hodgkin lymphoma, NHL, and have been implicated in drug resistance, aggression and poor prognosis. Chronic infection with hepatitis C, HCV, has been associated in some studies with increased risk of NHL. HCV is a widespread infection in the Egyptian population. Circulating free DNA (CFDNA) has been shown to be a good source of liver tissue-derived DNA in African and Asian patients with chronic liver disease or hepatocellular carcinoma, HCC. Our previous results have shown TP53 mutations in 5% of CFDNA and 10% of tumours of HCC, with underlying HCV. OBJECTIVE: Since previous studies have shown p53 mutations in the DNAs extracted from the NH lymphoid tumours, we have assessed the presence of p53 mutations from exons 5 to 9 in CFDNA in patients with NHL, from Alexandria, Egypt, where HCV is highly prevalent, in a first attempt case-control preliminary study. METHODS: CFDNA was extracted from sera of 20 cases with NHL and 20 negative control individuals. The retrieved serum DNAs were screened for TP53 mutations from exons 5 to 9 using direct sequencing and a PCR-restriction digestion analysis (RFLP). Concentrations of CFDNA were measured using Fluorometric assay. RESULTS: Concentrations of CFDNA were significantly higher among NHL patients compared to the negative control individuals indicating a very high release or turn-over of DNA from the tumour into the blood stream among NHL patients. Mutations of p53 determined in NHL cases (30%) were of Arg-176 (1/20: 5%), Phe-238 (1/20: 5%), Ser-249 (2/20; 10%), Lys-249 (1/20: 5%) and Phe-250 (1/20: 5%). No mutations were detected among controls. However, Arg-213 polymorphism was found in 2 cases of NHL (10%) and in 1 case of controls (5%). CONCLUSION: Our findings of higher DNA concentrations with some p53 mutations in CFDNA from patients with NHL that match the previous reported p53 mutations from tumour DNA may hold promises that CFDNA may serve as a convenient source of tumour-derived DNA to serve as a promising tool of a non-invasive, low-cost new strategy for earlier detection, diagnosis and follow up of the disease. A large-scale prospective study utilizing CFDNA and DNA from tumours of NHL patients will be required to validate this first trial of utilizing CFDNA from NHL patients.

Modulation of IL-4 level by fludarabine and its relation to apoptosis in chronic B-cell lymphocytic leukemia.

UNLABELLED: Accumulation of malignant B-lymphocytes in chronic B-cell lymphocytic leukemia (B-CLL) is mainly attributed to reduced apoptosis rather than increased proliferation rate. Interleukin-4 (IL-4) has been proved to be involved in the survival mechanisms of B-cells as well as protection of B-CLL cells against spontaneous or drug induced apoptosis. Fludarabine is one of purine analogs and the current standard treatment for B-CLL, which has been proved to induce apoptosis in normal and malignant lymphocytes. We investigated the effect of ex vivo treatment of peripheral blood lymphocytes (PBLs) with Fludarabine on apoptosis and IL-4 production in untreated patients with B-CLL. The study was conducted on 15 recently diagnosed B-CLL patients and 15 normal healthy control subjects. PBLs were isolated and cultured in complete culture media without and with the addition of 1 microM/ml Fludarabine for 48 hrs. Harvested cells were assessed by flowcytometry for apoptosis and IL-4 production using staining with Annexin-V/PI and specific monoclonal IL-4 antibody, respectively. RESULTS: Fludarabine significantly increased the rate of in vitro PBLs' apoptosis in both B-CLL patients and normal subjects (3.81 +/- 1.98% and 4.11 +/- 2.14% without Fludarabine vs 14.78 +/- 7.83% and 9.99 +/- 5.60% with Fludarabine, respectively). However, the cytotoxic effect of Fludarabine was significantly higher in B-CLL patients than normal control subjects. Cytolasmic IL-4 content, as reflected by mean flouresence intensity (MFI), as well as percentage of IL-4+ve PBLs in absence Fludarabine were nearly the same both in B-CLL patients (20.28 +/- 14.34 & 2.97 +/- 1.48%, respectively) and normal subjects (27.75 +/- 14.44 & 2.58 +/- 1.27% respectively), with no significant difference. Corresponding values were significantly increased in both B-CLL patients (34.46 +/- 22.95 & 15.08 +/- 8.17%, respectively) and normal subjects (40.15 +/- 17.11 & 17.05 +/- 8.74%, respectively) when PBLs were co-cultured with Fludarabine. However, no significant difference was observed when studied groups were compared to each other. No correlation was observed between the intracellular IL-4 content or percentage of IL-4+ve PBLs and Fludarabine-induced apoptosis. In conclusion, Floudarabine could induce apoptosis and IL-4 production in B-CLL patients. Further studies on large cohort population is recommended to clarify the apoptotic effect of Fludarabine.

Markers of apoptosis and proliferation related gene products as predictors of treatment outcome in childhood acute lymphoblastic leukemia.

The aim of the study is to characterize markers of apoptosis in children with acute lymphoblastic leukemia (ALL) in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 39 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL-2 and nuclear factor-kappa B (NF-kappaB); and flow cytometry for CD95, CD40, CD49d and CD11a. Apoptosis was significantly lower in patients than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those who achieved remission. Anti-apoptotic factors: CD40, BcL-2, and NF-kappaB were all found to be higher in cases than controls and in cases with no remission than those achieved remission. CD49d was significantly lower in cases than controls, and significantly lower in cases with who did not achieve remission. CD11a levels were similar in the various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and B lineage and is considered the most potent influencer and predictor of resistance to therapy. Inhibitors for the activity of CD40, Bcl-2 and NF-kappaB as well as stimulants to CD95 could have a potential therapeutic benefit.

Phenotypic analysis of bone marrow lymphocytes from children with acute thrombocytopenic purpura.

Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flow-cytometric analysis of acute lymphoblastic leukemia (ALL), because their immunophenotype is similar to B-precursor cell lymphoblasts. Immune-mediated thrombocytopenia is a clinical condition characterized by increased platelet destruction due to sensitization of platelets by autoantibodies. The aim of this study was to determine the incidence and clinical impact of bone marrow hematogones in cases of acute immune thrombocytopenic purpura (ITP) among children. This was done by immunophenotyping of bone marrow lymphocytes of ITP cases and controls and follow up of cases. This study was done on 25 cases of ITP, 12 females and 13 males, their age ranged from 2 to 13 years. A control group was included in the study, 15 cases of apparently healthy children with matching age and sex taken from among bone marrow donors. Cases and controls were subjected to bone marrow lymphocyte immunophenotyping with flow-cytometry to verify the presence of hematogones. A statistically significant increase in the percentage of hematogones was demonstrated in their bone marrows. An increased percentage of CD10+ lymphocytes was demonstrated; with a mean of 18+/-15.2%, CD19+ with a mean of 27+/-16.3% and CD34+ with a mean of 3.7+/-3.2%. No correlation was found between the percentage of hematogones and peripheral platelet count or bone marrow lymphocytic count. In conclusion, there is an increase in the bone marrow hematogones in ITP cases in comparison to normal controls. This could be the sequence of an immunological response to the cause which determined the disease, or the regeneration of the stem cell compartment following transient damage.

A novel gene, FGA7, is fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient with T-cell acute lymphoblastic leukemia.

AML1 is among the most frequent targets of chromosomal rearrangements in human leukemias. We report here the molecular analysis of a t(4;21)(q28;q22) that has disrupted AML1 in a patient with de novo T-cell acute lymphoblastic leukemia. By using 3'-RACE analysis, we show that this rearrangement results in the fusion of a novel gene immediately downstream of exon 5 or exon 6 of AML1, indicating that the AML1 breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The sequence of the novel gene, located at 4q28, does not have any significant homology with any of the known genes in the human GenBank DNA database. However, the first 118 bases are identical to a part of a human ovarian EST. Also, its high homology with mouse and rat sequences suggests that this sequence most probably represents a part of a novel gene, which we named FGA7 (Fused Gene 7 to AML1). Following the AML1 open reading frame, the FGA7 sequence encodes an unknown protein of 27 amino acids. We isolated three bacterial artificial chromosome (BAC) clones that contain the FGA7 sequence and confirmed the breakpoint of the gene on the patient's metaphase spreads by fluorescence in situ hybridization using these BACs as probes. RT-PCR and Northern blot analyses revealed that FGA7 is expressed in ovarian and skeletal muscle tissues. The predicted AML1-FGA7 chimeric proteins contained a limited number of residues fused to AML1 in a situation similar to that reported for the AML1-EAP fusion that is a product of t(3;21). It is possible that the expression of a constitutively shortened AML1 could compete with full-length AML1 and act as a dominant negative inhibitor of the promoters that the core binding factor activates.